Method of making 5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide

ABSTRACT

This method of making 5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide is based on the use of an oxathiolane, namely, 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide, which may be formed by condensing 2-mercaptoethanol with acetoacetanilide under acidic conditions in a solvent medium (aromatic hydrocarbon, chlorinated hydrocarbon or alkyl ester of an aliphatic acid). The said oxathiolane, with or without purification, is reacted with hydrogen peroxide in water or in a water-organic solvent mixture under basic conditions in the presence of a catalytic amount of a metal compound such as sodium tungstate to form 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide 3-oxide. The said oxathiolane oxide, while dissolved in a chlorinated hydrocarbon or an alkyl ester of an aliphatic carboxylic acid, or while suspended in an aromatic hydrocarbon, is subjected to a ring expansion reaction by heating under acidic conditions in the presence of a catalytic quantity of a sulfonium, sulfoxonium or phosphonium compound, to form 5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide with evolution of water. The product is a known bactericide and fungicide.

This invention relates to a method of making5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide, whichis aknown bactericide and fungicide.

The method of the invention involves the use of an oxathiolaneintermediate [formed by condensing mercaptoethanol (I) withacetoacetanilide (II) under acidic conditions to form the intermediate2-methyl-N-phenyl-1,3-oxathiolane-3-acetamide (III)] which is thenoxidized under basic conditions to its 3-oxide (IV), and thereafterconverted by a ring expansion reaction under acidic conditions to5,6-dihydro-2-methyl-N-phenyl,-1, 4-oxathiin-3-carboxamide (V),according to the following equations: ##STR1##

U.S. Pat. No. 3,393,202, July 18, 1968, Kulka et al, disclosesconventional methods of making5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide, involving theuse of chlorinating agents and producing noxious by-products which areecologically undesirable.

Canadian Pat. No. 1,036,167, W. S. Lee, Aug. 8, 1978, disclosessynthesis of dihydro-1,4-oxathiins by rearrangement of 1,3-oxathiolanesulfoxides. The present invention provides an improved process.

The invention is concerned with a method of making5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide comprising thesteps of:

(A) providing an intermediate oxathiolane, preferably by bringingtogether 2-mercaptoethanol and acetoacetanilide in at least one organicsolvent selected from the group consisting of (a) aromatic hydrocarbonsolvent, (b) chlorinated hydrocarbon solvent, and (c) a solvent which isan alkyl ester of an aliphatic acid, in the presence of a catalyticquantity of a dehydrating acid, and heating the resulting mixture at atemperature of 45°-70° C. while removing evolved water of reaction,whereby 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide is formed;

(B) bringing together the 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamideand hydrogen peroxide under basic conditions in the presence of acatalytic quantity of a heavy metal compound, in a medium comprisingwater, or water plus organic solvent as defined in step (A) above,whereby 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide 3-oxide is formed;

(C) bringing together the 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide3-oxide and a catalytic quantity of a sulfonium, sulfoxonium orphosphonium compound under acidic conditions in organic solvent asdefined in step (A) above, and heating the mixture at a temperature of45°-80° C., while removing evolved water of reaction, and thereafterrecovering from the reaction mixture the thus formed5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide.

The 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide (III) intermediateformed in Step A can be purified and isolated, but is preferablyconverted directly to the corresponding2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide 3-oxide (IV) by the actionof aqueous hydrogen peroxide in Step B. This oxidation is carried outunder basic conditions in the presence of catalytic quantities of aheavy metal compound such as sodium tungstate in an effective mixture ofa suitable organic solvent and water or water alone.

The oxathiolane oxide (IV) is converted, preferably without isolation orpurification, to the oxathiin (V) in Step C by a thermal ring expansionreaction carried out in a suitable solvent under acidic conditions inthe presence of a catalytic quantity of a sulfonium, sulfoxonium orphosphonium compound, such as trimethylsulfonium iodide,tetrabutylphosphorium bromide, trimethylsulfoxonium iodide,triphenylpropylphosphonium bromide, and the like. In the absence of theonium compound the reaction proceeds at a slower rate and the yields aremarkedly lower due to decomposition of IV.

Suitable nonprotic solvents which can be used individually, or possiblyin combinations, for individual stages or the entire reaction sequenceare:

(a) aromatic hydrocarbons having a boiling point not greater than 145°C., e.g., benzene, toluene, xylene;

(b) chlorinated hydrocarbons having a boiling point not greater than130° C., e.g., chloroform;

(c) solvents having a boiling point not greater than 130° C. which arealkyl esters of aliphatic acids, e.g., isopropyl acetate or n-butylacetate.

The preferred solvent is toluene. Benzene is toxic and is not preferred.

The phenyl group of the starting compound (and consequently of the finalproduct) may be substituted if desired with one or more non-interferingsubstituents, such as at least one lower alkyl or lower alkoxysubstituent.

The present process is highly advantageous compared to certain otherproposed processes which require multiple changes of solvent withassociated losses and increased pollution control burden. The necessityof constant solvent change also results in a labor intensive andexpensive process. By contrast the present process can be carried outentirely in the same medium or at most involves only minimal change ofsolvent. It does not involve any expensive and difficult to removedimethylformamide (boiling point about 153° C.). Certain prior processesinvolving the use of benzene (a toxic solvent) depend upon a co-solvent(dimethylformamide) without which extensive decomposition of theoxathiolane 3-oxide occurs, with resultant low yields of oxathiin (V).

Certain proposed processes, as described in the above-cited CanadianPat. No. 1,036,167 of Lee, are relatively non-productive in that theyinvolve working in dilute solutions which result in small quantities ofproduct made in any one run. Furthermore the cycle times involved are solong as to render the productivity uneconomic. By contrast the presentprocess is operable in high concentration and short reaction times sothat productivity more than 40 times greater is possible.

The present method of obtaining the oxathiolane oxide (IV) avoids theuse of acetic acid, a protic solvent, and thus offers the followingadvantages: (1) a non-productive solvent change is avoided; (2) thereare no costs for acetic acid, caustic soda to neutralize this acid, norfor disposal of the resulting sodium acetate in an ecologically soundmanner. By contrast, the nonprotic solvent system employed in thepresent invention allows the use of hydrogen peroxide alone catalyzed bytraces of heavy metal compound such as sodium tungstate which is readilyrecyclable giving only water as by-product.

The present process involves the use of various oniom compounds asdefined above as effective catalysts in the formation of the oxathiin(V) in Step C. These catalysts can be used in minute quantities. Certainother processes do not involve the use of catalysts other thanp-toluene-sulfonic acid but instead involve a mixture of solvents withdimethylformamide which is expensive and difficult to recover because ofits high boiling point.

In typical practice of Step A of the invention, acetoacetanilide (II) isreacted with 2-mercaptoethanol (I) in one of three types of solvents:(a) aromatic hydrocarbons, e.g., toluene (b) chlorinated hydrocarbons,e.g., chloroform (c) alkyl esters of aliphatic acids, e.g., isopropylacetate or n-butyl acetate. Typically, between 0.5-6 liters of solventmay be used per kilogram of rectants [acetoacetanilide(II)+2-mercaptoethanol (I)]. Trace amounts (e.g., 0.5-8% by weight ofreactants) of acid dehydration promoter such as p-toluenesulfonic acidor 2-naphthalenesulfonic acid may be used to catalyze the reaction. Therelative proportions of acetoacetanilide and 2-mercaptoethanol are notcritical; equimolar or approximately equimolar proportions are suitablebut an excess of one of the other of the reactants may also be present.Frequently it is advantageous to use a slight excess of2-mercaptoethanol.

The reaction between the acetoacetanilide and the 2-mercaptoethanol ispreferably carried out at a temperature of 45°-70° C. For convenience inremoving the water of reaction, it is preferable to reflux the reactionmixture during the process. With most of the solvents employed, thismeans conducting the reaction under reduced pressure, except when thesolvent is chloroform which boils at about 60° C.

Reaction temperatures greater than about 70° C. are deleterious to yielddue to side reactions. The reaction time frequently varies from 2 to 8hours.

At the conclusion of the reaction between I and II two alternative arepossible. Alternative (i), which is preferred, comprises the conversionof the oxathiolane (III) in the reaction mixture directly to oxathiolaneoxide (IV) in Step B without purification. A direct conversion isusually the most productive sequence. Toluene is frequently thepreferred solvent.

Alternative (ii), which involves purification, ordinarily requires achange of solvents prior to oxidation of oxathiolane (iii) tooxathiolane oxide (IV) is Step B. It typically comprises a base wash(e.g., saturated aqueous sodium bicarbonate solution), phase separation,drying over a desiccant (e.g., magnesium sulfate), filtration andreduction in volume. To achieve high yields a diluent (e.g., toluene,methylene chloride) is ordinarily added prior to the base wash if thesolvent of choice is toluene and less than 2 liters of toluene perkilogram of reactants were used to carry out the condensation reaction.

Step B, the conversion of oxathiolane (III) to oxathiolane oxide (IV),is accomplished by a heterogeneous reaction with aqueous hydrogenperoxide in an effective mixture of a suitable organic solvent (i.e., aspreviously described) and water or water alone. The exact proportions ofsolvent, water and oxathiolane (III) are not critical and may varyconsiderably depending upon the solubility of oxathiolane (III) in theorganic solvent. It will be understood that the amount of organicsolvent that is most appropriate ordinarily varies inversely with thesolubility of oxathiolane (III) in that organic solvent. Thus, tocomplete the oxidation about 0.6 liter chloroform per kilogram ofoxathiolane (III) might be used versus about 1-1.5 liters toluene perkilogram of oxathiolane (III). In any event, there will ordinarily notbe more than about 4 liters (e.g., 0.5-4 liters) of liquid medium(water, or water plus solvent), preferably not more than about 2 liters,present per kilogram of oxathiolane in this oxidation step. Usually theliquid medium comprises at least 10% water by weight.

The pH of the aqueous phase in Step B must be maintained at greater than7 and preferably in the range of 8-9. This suppresses the reversion ofoxathiolane (III) to the starting materials I and II. Any appropriatebase may be used to control the pH, including the organic and inorganicbases, of which particularly convenient suitable examples are sodiumbicarbonate, sodium acetate, sodium formate and sodium hydroxide. Therequired amount of the base is conveniently dissolved in one liter ofwater per four kilograms of oxathiolane oxide (IV). When Alternative(ii) (Step A) is followed, it is advantageous to use saturated (6-8% byweight) sodium bicarbonate solution [1 liter per 4 kilograms ofoxathiolane oxide (IV)]. When Alternative (i) (Step A) is followedadditional base (e.g., sodium hydroxide) is appropriately added tocompensate for the p-toluenesulfonic acid used as catalyst in Step A.

The oxidation step is carried out with the aid of a heavy metal compoundoxidation catalyst, notably a metal (including alkali metal and alkalineearth metal), ammonium or amine salt of tungstic or molybdic acid, or azirconium compound, especially a zirconium salt, such as zirconiumtetrachloride or zirconium tetranitrate. The preferred catalysts are themetal salts of tungstic and molybdic acid. The most preferred catalystis sodium tungstate. Catalytic concentrations are usually about 0.1 orless to 2 or more percent by weight based on the weight of theoxathiolane. Without such a catalyst the reaction proceeds only slowlyor not at all in the media described above.

The oxidation step is carried out with very vigorous stirring attemperatures ranging from 0°-25° C. approximately. Since the reaction isexothermic, cooling is appropriate in the early stages. Control of thereaction is facilitated by gradual addition of the oxidizing agent, soas to avoid an excessive exotherm, particularly at the start. It isparticularly advantageous to carry out the Step B reaction in twostages; in the first stage, which typically lasts 1 to 3 hours, thetemperature is ordinarily maintained at 0°-10° C., while in the secondstage, which also commonly lasts 1 to 3 hours, the temperature may bepermitted to rise into the upper end (e.g., 20°-25° C.) of the reactiontemperature range. Slow addition of 35% hydrogen peroxide (othercommercial grades, e.g., 30-70% may be used) is carried out during theinitial part of the first stage (e.g., on a laboratory scale, dropwiseaddition over a period of 10 to 30 minutes). Ordinarily an amount ofperoxide approximately equivalent to (usually slightly in excess of) theoxathiolane (III) is used.

A simple phase separation completes the reaction sequence in the caseswhere the solvent of choice is either a chlorinated hydrocarbon or analkyl ester of an aliphatic acid. A quantity of methylene chloride(ordinarily the minimum quantity necessary to achieve a two-phasesystem, e.g., 10-100% by volume of the reaction mixture) isappropriately added when the solvent of choice is an aromatichydrocarbon. In any case, the aqueous phase is discarded or recycled (torecover sodium tungstate). The organic phase is dried over a desiccant(e.g., magnesium sulfate) or by azeotropic distillation of a portion ofthe solvent to remove the water present. In the cases where the solventof choice is either a chlorinated hydrocarbon or alkyl ester of anyaliphatic acid the dried solutions are suitable for Step C. Thetoluene/methylene chloride/oxathiolane oxide (IV) solution is reduced involume to remove the methylene chloride present to made oxathiolaneoxide (IV) suitable for Step C. If desired, this reduction in volume ofthe toluene/methylene chloride/oxathiolane oxide (IV) solution may becombined with the initial step of Step C.

Oxathiolane oxide (IV) prepared by the sodium tungstate/hydrogenperoxide method is a heat sensitive syrup ordinarily consisting of amixture of cis/trans isomers typically in the ratio of about 2:1respectively. Oxathiolane oxide (IV) readily undergoes decomposition attemperatures greater than about 50° C. or in the presence of acids;therefore, all reductions in volume are appropriately carried out atreduced pressures under neutral or slightly basic conditions.

To carry out Step C oxathiolane oxide (IV) is dissolved (if not alreadyin solution) in a suitable solvent consisting essentially of either achlorinated hydrocarbon or an ester of an aliphatic acid or suspended ina medium consisting essentially of an aromatic hydrocarbon usually in anamount ranging for example from 1-12 liters of solvent per kilogram ofoxathiolane oxide (IV). An effective mixture of a dehydrating acid(e.g., p-toluenesulfonic acid, methanesulfonic acid, phosphoric acid or2-naphthalenesulfonic acid) and an onium compound (sulfonium,sulfoxonium or phosphonium) is added. Typical onium compounds may berepresented by the formula

    (O←).sub.m Z.sup.+ (R).sub.n X.sup.-

where X is a halogen (fluorine, chlorine, bromine or iodine) or theanion of methane sulfonic or paratoluenesulfonic acids, the R's arechosen from the group consisting of alkyl (usually C₁ -C₁₆), phenyl(unsubstituted or substituted wih a non-interfering substituent) andbenzyl, and may be the same or different, Z is phosphorus or sulfur, mis zero when Z is phosphorus and zero or 1 when Z is sulfur, and n is 4when Z is phosphorus and 3 when Z is sulfur. Ordinarily initialquantities of the dehydrating agent and onium catalyst are employed inweight ratio of about 1:20 but other ratios are suitable. Remarkablysmall quantities [e.g., 0.25 percent or less to 3 percent or more, byweight based on the oxathiolane oxide (IV)] are effective. The resultingsolution (suspension) is subjected to a moderately elevated temperature,sufficient to cause the reaction to proceed at a reasonable rate but notso high as to cause decomposition. A reaction temperature of 40°-80° C.is usually satisfactory. The water formed as the reaction proceeds isremoved in a suitable manner, for example by refluxing under aseparating device such as a Dean and Stark trap. Such refluxing may beperformed under reduced pressure to avoid heating to an excessivetemperature. A typical refluxing temperature range is 45°-50° C. Anadditional amount of p-toluenesulfonic acid [e.g., one percent by weightof oxathiolane oxide (IV)] is typically added and refluxing is continuedfor an hour or so at 45°-50° C., followed by a longer period (e.g., 2 to4 hours) of refluxing at a higher temperature (e.g., 75°-80° C., exceptwhen chloroform [which boils at about 60° C.] is used). About 30% of thewater of reaction is generated in the initial state, the remainder atthe elevated temperature. It may be advantageous to wash the reactionmixture with dilute acid (e.g., hydrochloric acid) just prior to thefinal heating stage. The solution is cooled to about 20° C., washed withan aqueous 10% sodium hydroxide solution [about 200 ml per gram mole ofoxathiolane (III)], and the organic phase dried over a desiccant (e.g.,magnesium sulfate) and reduced in volume under vacuum. The residue isthen typically recrystallized from a suitable solvent, usually eithercold toluene or cold isopropyl alcohol (e.g., 3 ml of solvent per gramof residue). The preferred method is to carry out the reaction sequencein toluene, wash with base, cool the toluene later to precipitate theoxathiin (V), filter, and dry.

Typical cycle times (actual reaction time excluding time formanipulations such as solvent removal, phase separation, etc.) are asfollows:

    ______________________________________                                        Cycle Times (Hours)                                                                                            Most                                         Step    Broad       Preferred    Preferred                                    ______________________________________                                        A       1-10        2-6          2-4                                          B       1-6         1-4          1-3                                          C       2-15         2-10        2-7                                          ______________________________________                                    

The following examples will serve to illustrate the practice of theinvention in more detail.

EXAMPLE 1

A mixture of toluene (1200 ml), p-toluenesulfonic acid monohydrate (12g), 2-mercaptoethanol (330 g, 4.225 moles) and acetoacetanilide (709.2g, 4 moles) is refluxed under a Dean and Stark trap for 5.5 hours at60°-65° C. at a pressure of about 140 mm Hg. The reaction mixture iscooled to 25° C., methylene chloride added (1000 ml), and the resultingsolution washed with aqueous saturated sodium bicarbonate solution (400ml). The organic layer is separated, dried over magnesium sulfate,filtered, and reduced in volume under vacuum. Yield 936 g (98.6%) ofoxathiolane (III).

A mixture of oxathiolane (III) (48.8 g, 0.205 mole) (prepared above),toluene (73.2 ml), saturated sodium bicarbonate (10.21 ml) and water (2ml) containing sodium tungstate dihydrate (0.19 g), is stirredvigorously and treated dropwise with hydrogen peroxide (19.9 ml, 0.215mole) a 0°-5° C. The mixture is stirred for 2 hours at 0°-5° C., and for2 hours at 20°-25° C. A minimum (175 ml) of methylene chloride is addedto achieve a two-phase system. The aqueous phase is separated and washedwith a small portion of methylene chloride. The organic layers arecombined, dried over magnesium sulfate, and reduced in volume undervacuum.

A mixture of crude oxathiolane oxide (IV) [prepared as above fromoxathiolane (III) (56.6 g, 0.238 mole)], toluene (191.2 ml),trimethylsulfonium iodide (1.1 g), and p-toluenesulfonic acidmonohydrate (0.047 g) is heated at reflux under a Dean and Stark trap at50° C. at a pressure of about 80 mm Hg for 3 hours. Additionalp-toluenesulfonic acid monohydrate (0.72 g) is added and the solutionrefluxed for 1 hour at 50° C. followed by reflux at 80° C. for 3 hours.The reaction mixture is cooled and washed with aqueous 10% sodiumhydroxide solution (20 ml), cooled and filtered. Recrystallization fromisopropyl alcohol gives a first crop yield of 26.8 (0.114 mole, 44.7%)of oxathiin (V) based on acetoacetanilide (II).

EXAMPLE 2

Oxathiolane (III) (56.0 g, 0.235 mole) is prepared and converted tooxathiin (V) (27.6 g, 0.117 mole) as described in Example 1 utilizingtetra(n-butyl)phosphonium bromide (1.1 g) in place of trimethylsulfoniumiodide. Yield 49.7% based on acetoacetanilide.

EXAMPLE 3

Oxathiolane (II) (52.1 g, 0.219 mole) is prepared and converted tooxathiin (V) (25.0 g, 0.106 mole) as described in Example 1 utilizingtrimethylsulfoxonium iodide (1.1 g) in place of trimethylsulfoniumiodide. The mother liquor after having been washed with 10% sodiumhydroxide, is separated, reduced in volume under vacuum andrecrystallized from isopropyl alcohol. Yield 48.4% based onacetoacetanilide.

EXAMPLE 4

Oxathiolane (III) (57.2 g, 0.241 mole) is prepared and converted tooxathiin (V) (18.9 g, 0.080 mole) as described in Example 1 utilizingtriphenyl n-propyl phosphonium bromide (1.1 g) in place oftrimethylsulfonium iodide. The mother liquor after having been washedwith 10% sodium hydroxide, is separated, reduced in volume under vacuumand recrystallized from isopropyl alcohol. Yield 33.2% based onacetoacetanilide.

What is claimed is:
 1. A method of making5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide comprising thesteps of:(A) providing 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide;(B) bringing together the 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamideand hydrogen peroxide under basic conditions, in the presence of acatalytic quantity of a suitable heavy metal compound oxidation catalysteffective of catalyze the oxidation of said2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide by the said hydrogenperoxide, in a liquid medium comprising water, or water plus at leastone nonprotic organic liquid selected from the group consisting of (a)aromatic hydrocarbon solvent having a boiling point not greater than145° C., (b) chlorinated hydrocarbon solvent having a boiling point notgreater than 130° C., and, (c) a solvent having a boiling point notgreater than 130° C. which is an alkyl ester of an aliphatic carboxylicacid, and subjecting the resulting mixture while agitating to atemperature of from 0° to 25° C., whereby2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide 3-oxide is formed; (C)bringing together the 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide3-oxide and a catalytic quantity of a sulfonium, sulfoxonium orphosphonium compound under acidic conditions in a nonprotic organicliquid as defined in step (B) above, and heating the mixture at atemperature of 45° to 80° C. while removing evolved water of reaction,and thereafter recovering from the reaction mixture the thus formed5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide, the saidsulfonium, sulfoxonium or phosphonium catalyst being an onium compoundof the formula

    (O←).sub.m Z.sup.+ (R).sub.n X.sup.-

where X is a halogen or the anion of methanesulfonic orp-toluenesulfonic acids, the R's are chosen from the group consisting ofC₁ -C₁₆ alkyl, phenyl and benzyl, Z is phosphorus or sulfur, m is zerowhen Z is phosphorus and zero or 1 when Z is sulfur, and n is 4 when Zis phosphorus and 3 when Z is sulfur.
 2. A method as in claim 1 in whichstep (C) is carried out directly on the mixture resulting from step (B)without changing solvent.
 3. A method as in claim 1 in which the2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide in step (A) is provided inthe form of an in-situ reaction product of 2-mercaptoethanol andacetoacetanilide prepared in an organic solvent as speficied in step(B).
 4. A method as in claim 3 in which steps (A), (B) and (C) arecarried out in the same organic solvent.
 5. A method as in claims 1 or 4in which the solvent is xylene, toluene, chloroform, isopropyl acetateor n-butyl acetate.
 6. A method as in claim 1 in which, in step (B), theliquid medium comprises at least 10% water by weight.
 7. A method as inclaim 1 in which there is not more than 4 liters of liquid mediumpresent per kilogram of said oxathiolane in step (B).
 8. A method as inclaim 1 in which the pH of the reaction mixture in step (B) is 8 to 9.9. A method as in claim 1 in which the heavy metal compound is a metalsalt of tungstic or molybdic acid.
 10. A method of making5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide comprisingbringing together 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide 3-oxideand a catalytic quantity of a sulfonium, sulfoxonium or phosphoniumcompound under acidic conditions in at least one nonprotic organicliquid selected from the group consisting of (a) aromatic hydrocarbonsolvent having a boiling point not greater than 145° C., (b) chlorinatedhydrocarbon solvent having a boiling point not greater than 130° C.,and, (c) a solvent having a boiling point not greater than 130° C. whichis an alkyl ester of an aliphatic carboxylic acid, and heating themixture at a temperature of 45° to 80° C. while removing evolved waterof reaction, and thereafter recovering from the reaction mixture thethus formed 5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide,the said sulfonium, sulfoxonium or phosphonium catalyst being an oniumcompound of the formula

    (O←).sub.m Z.sup.+ (R).sub.n X.sup.-

where X is a halogen or the anion of methanesulfonic orp-toluenesulfonic acids, the R's are chosen from the group consisting ofC₁ -C₁₆ alkyl, phenyl and benzyl, Z is phosphorus or sulfur, m is zerowhen Z is phosphorus and zero or 1 when Z is sulfur, and n is 4 when Zis phorphorus and 3 when Z is sulfur.
 11. A method as in claim 10 inwhich the catalyst is a sulfonium compound.
 12. A method as in claim 11in which the sulfonium compound is trimethylsulfonium iodide.
 13. Amethod as in claim 10 in which the catalyst is a sulfoxonium compound.14. A method as in claim 13 in which the sulfoxonium compound istrimethylsulfoxonium iodide.
 15. A method as in claim 10 in which thecatalyst is a phosphonium compound.
 16. A method as in claim 15 in whichthe phosphonium compound is tetrabutylphosphonium bromide ortriphenylpropylphosphonium bromide.
 17. A method of making5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide comprising thesteps of:(A) preparing 2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide bybringing together 2-mercaptoethanol and acetoacetanilide in a nonproticorganic solvent liquid selected from the group consisting of (a)aromatic hydrocarbon solvent having a boiling point not greater than145° C., (b) chlorinated hydrocarbon solvent having a boiling point notgreater than 130° C., and, (c) a solvent having a boiling point notgreater than 130° C. which is an alkyl ester of an aliphatic carboxylicacid, in the presence of p-toluenesulfonic acid or 2-naphthalenesulfonicacid in amount sufficient to catalyze the condensation reaction of the2-mercaptoethanol and acetoacetanilide, heating the reaction mixture toa temperature of 45° to 70° C., and removing the water of condensationformed by said reaction, whereby2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide intermediate is formed;(B) without recovery of the2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide from the reaction mixtureof step (A), adding a base to the said reaction mixture to produce a pHwithin the range 8 to 9, and gradually adding aqueous hydrogen peroxideto the resulting basic mixture in the presence of a heavy metal compoundoxidation catalyst selected from the group consisting of metal salts oftungstic acid, metal salts of molybdic acid and zirconium salts in anamount effective to catalyze the oxidation of the said oxathiolaneintermediate by the hydrogen peroxide, and maintaining the mixture at atemperature of 0° to 25° C. while agitating the mixture whereby2-methyl-N-phenyl-1,3-oxathiolane-2-acetamide 3-oxide is formed; (C)separating the organic phase of the mixture resulting from step (B),drying said organic phase, and without recovering the said 3-oxideadding to said organic phase p-toluenesulfonic acid or2-naphthalenesulfonic acid and an onium compound selected from the groupconsisting of trimethylsulfonium iodide, tetrabutylphosphonium bromide,trimethylsulfoxonium iodide and triphenylpropylphosphonium bromide, inamounts sufficient to catalyze evolution of water and ring expansion ofthe said 3-oxide, heating the mixture at a temperature of 45° to 80° C.,and removing evolved water of reaction whereby the desired5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide is formed. 18.A method as in claim 17 in which the said nonprotic organic solvent is(a) an aromatic hydrocarbon having a boiling point not greater than 143°C. and there is added to the reaction mixture at the conclusion of step(B) a quantity of methylene chloride equal to from 10 to 100% by volumeof the reaction mixture prior to separating the organic phase for step(C).
 19. A method as in claim 18 in which, after separating the saidorganic phase, the methylene chloride is evaporated prior to undertakingstep (C).
 20. A method as in claim 17 in which step (C) is carried outat a temperature within the range of 45° to 50° C. until 30% of thetheoretical quantity of water of reaction has been generated, andthereafter the reaction mixture is heated at a higher temperature of 75°to 80° C.
 21. A method as in claim 20 in which the reaction mixture iswashed with dilute acid prior to heating at said higher temperature. 22.A method as in claim 17 in which the amount of liquid medium presentis:between 0.5 and 6 liters per kilogram of acetoacetanilide andmercaptoethanol in step (A); between 0.5 and 4 liters per kilogram ofsaid oxathiolane in step (B); and between 1 and 6 liters per kilogram ofsaid 3-oxide in step (C).
 23. A method as in claim 17 in which the saidsolvent is toluene.
 24. A method as in claims 17 or 23 in which theoxidation catalyst is sodium tungstate.